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Published on: February 17, 2022
Achieving theranostic probes targeting BRD3/BRD4 for imaging and therapy of tumor
Yuqi Gao1, Qiao Liu2, Cong Song3
1School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, China.
Abstract:
The BET family proteins play pleiotropic roles in the tumorigenesis and growth of various human malignancies that have aroused great interests as the cancer therapeutic targets. Therefore, it's significant to develop labeling toolkits for the dynamic monitoring of BET family proteins in living tumor cells and tissue slices. In particular, there are few small-molecule fluorescent probes based on BET family proteins developed for real-time imaging of these proteins in tumor cells and tissues and treatment of breast cancer. In general, antibodies of BET family proteins are chosen for imaging of these proteins. However, the cost of these antibodies is more expensive than small molecules and the operation is relatively complicated. Moreover, the antibodies for imaging are not capable of the therapy for breast cancer. Thus, it's essential to exploit a novel imaging system for BET family proteins which is easy-operating and economical, with achieving therapeutic effects simultaneously. Therefore, a series of fluorescent probes (17-21) targeting BET family proteins were developed. Through the evaluation studies, probe 17 showed advantages in docking studies, analysis of cell viability, and imaging studies. Importantly, probe 17 was capable of distinguishing tumor cells and tissue slices and made a distinction between them by labeling BRD3 and BRD4 proteins. Importantly, probe 17 showed higher resolution in mouse tumor and human tumor slice imaging than BRD3 and BRD4 antibodies. Moreover, compared with these antibodies, probe 17 was more stable, more economical and easier to operate in the imaging assays. In addition, it also played an anti-tumor role by inducing cell apoptosis, proliferation inhibition, and cycle arrest in tumor cells. All these features render probe 17 to perform as an effective labeling toolkit compatible for imaging studies of BRD3/BRD4, as well as an approach to diagnosis and treatment of breast cancer.
Insights
A new fluorescent probe, designated probe 17, enables real-time imaging of BET proteins in cancer cells and tissues. This economical probe also demonstrates anti-tumor effects, offering a dual approach for breast cancer diagnosis and treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- BET family proteins are crucial in tumorigenesis and are key cancer therapeutic targets.
- Existing imaging methods for BET proteins often rely on expensive and complex antibodies.
- There is a need for economical, easy-to-operate fluorescent probes for BET protein imaging and cancer therapy.
Purpose of the Study:
- To develop novel small-molecule fluorescent probes for dynamic monitoring of BET family proteins.
- To evaluate the efficacy of these probes in imaging and potential therapeutic applications for breast cancer.
- To identify a probe superior to antibodies in terms of cost, ease of use, and performance.
Main Methods:
- Synthesis and evaluation of a series of fluorescent probes (17-21) targeting BET family proteins.
- In vitro studies including docking, cell viability assays, and fluorescence imaging in tumor cells and tissue slices.
- Comparative analysis of probe 17 against BRD3 and BRD4 antibodies for imaging resolution, stability, and operational simplicity.
- Assessment of probe 17's anti-tumor activity, including apoptosis induction, proliferation inhibition, and cell cycle arrest.
Main Results:
- Probe 17 demonstrated superior performance in docking studies, cell viability, and imaging compared to other synthesized probes.
- Probe 17 effectively distinguished tumor cells and tissues by labeling BRD3 and BRD4 proteins.
- Imaging studies showed probe 17 offered higher resolution than antibodies in mouse and human tumor samples.
- Probe 17 exhibited enhanced stability, cost-effectiveness, and ease of operation over antibodies.
- Probe 17 exhibited significant anti-tumor effects, inducing apoptosis, inhibiting proliferation, and causing cell cycle arrest.
Conclusions:
- Probe 17 serves as an effective and economical toolkit for imaging BRD3/BRD4 proteins in biological samples.
- The probe's dual capability for imaging and therapeutic intervention presents a promising approach for breast cancer diagnosis and treatment.
- Probe 17 offers a significant advancement over traditional antibody-based methods for BET protein analysis and cancer therapy.
